Genetic and biochemical studies show that changes in growth response of poliovirus to guanidine is generally accompanied by alterations in viral capside proteins. Deletion mutants (DI particles) of poliovirus that lack 15% of the viral genome and a large portion of the capsid locus can infect cells, produce DI-specific RNA, but fail to synthesize detectable capsid polypeptides. The normal precursor of capsid proteins, NCVPla, is replaced with an unstable protein, DI-P, that is rapdily degraded. Nevertheless, DI-specific RNA synthesis is blocked by guanidine. Either low levels of DI-P or capsid polypeptide sequences found in degradative oligopeptides account for sensitivity of DI-specific RNA guanidine or a second locus on the viral chromosome is a determinant of guanidine sensitivity along with capsid polypeptides. The proposed research will determine: 1. Whether guanidine resistant variants of DI particles can be reproducibly selected from guanidine sensitive stocks of DI particles. 2. The physico-chemical and growth properties of a new DI particle (termed Dx). After 40 passages in the presence of guanidine the DI particle originally present (D3) disappeared and a new D particle with a smaller deletion appeared. Is the Dx particle resistant to guanidine? Does the Dx mutant produce any complete capsid polypeptides? Where is the deletion located on the chromosome of the D particle? Is the deletion distinct or heterogeneous?